【摘要】：無論在平時或戰(zhàn)時,顱腦創(chuàng)傷在全身各類創(chuàng)傷的發(fā)生率上居第2位,僅次于四肢傷,而其死亡率卻居首位。在美國,顱腦創(chuàng)傷發(fā)生率為每10萬人口就有200人患病,新發(fā)顱腦創(chuàng)傷病人每年大約50萬,其中約有2萬人死亡,3萬人致殘。而在我國,新發(fā)顱腦創(chuàng)傷病人每年大約60萬人,其中死亡人數(shù)達10萬之眾,造成直接和間接經(jīng)濟損失達100億元以上。而在臨床上合并SAH的顱腦外傷占到39%-65%,故而在臨床上將顱腦損傷后,腦組織挫裂傷,腦底部或腦表面皮層細小血管損傷出血,直接流入蛛網(wǎng)膜下腔的這一臨床綜合征定義為創(chuàng)傷性蛛網(wǎng)膜下腔出血。并根據(jù)其血液分布情況將其分為腦表面蛛網(wǎng)膜下腔型、顱底蛛網(wǎng)膜池型及腦表面和顱底蛛網(wǎng)膜池混合型三型。CVS的發(fā)生影響腦功能區(qū)的供血供氧,導致大腦相應(yīng)功能部分或全部喪失,影響患者生活質(zhì)量及預(yù)后。Graham等發(fā)現(xiàn),在創(chuàng)傷性顱腦損傷死亡病人中,約有90%的病人腦組織有缺血性改變。而CVS的發(fā)生率在tSAH患者中高達67%。Hanlon等研究證實創(chuàng)傷性蛛網(wǎng)膜下腔出血是中、重型顱腦損傷病人較多發(fā)生的征象之一。有些文獻認為顱腦損傷后伴有創(chuàng)傷性蛛網(wǎng)膜下腔出血者一般預(yù)后不良。尼莫地平是1、4-二氫吡啶類鈣通道拮抗劑,脂溶性較高,能較為順利通過血腦屏障,選擇性阻滯細胞膜上鈣離子通道開放,減少細胞外鈣離子大量內(nèi)流,抑制腦血管平滑肌的收縮,同時增強Ca2+—ATP酶活性,增加細胞內(nèi)鈣離子排出,減輕細胞內(nèi)鈣離子超載,保護神經(jīng)細胞,并且尼莫地平對腦血管有高度選擇性,改善腦動脈血流量的效果遠大于外周血管,對大腦損傷區(qū)灌流不足部位灌注量的增加通常高于正常區(qū)域,故而不會產(chǎn)生腦內(nèi)盜血現(xiàn)象。而以往的相關(guān)研究已證實,尼莫地平是目前唯一的,具有循證醫(yī)學支持的,對aSAH后CVS有防治作用的有效藥物。而對于tSAH引起的CVS有無相同療效,醫(yī)學界里盡管進行了很多研究,但目前尚無明確的定論。 目的 利用持續(xù)顱內(nèi)壓監(jiān)測、TCD、GCS、GOS來分析尼莫地平在預(yù)防tSAH后CVS發(fā)生和改善tSAH預(yù)后方面的臨床效果,從而為其臨床應(yīng)用提供理論依據(jù)。材料與方法 1.病例納入和排除標準：(1)納入標準：急性顱腦損傷,傷后6h內(nèi)入院；頭部CT顯示蛛網(wǎng)膜下腔出血；320排頭顱CT血管造影排除動脈瘤破裂出血；幕上血腫量30ml,幕下血腫10ml,中線移位5mmm；年齡18-65歲；入院GCS評分為6-12分。(2)排除標準：槍傷及開放性顱腦損傷；合并嚴重彌漫性軸索損傷、嚴重肝腎功能不全者；收縮壓持續(xù)低于100mmHg達1h以上；孕婦；發(fā)病前兩周或在臨床試驗中有尼卡地平或其他鈣離子拮抗劑用藥史的患者；中途病情變化需開顱手術(shù)或停止試驗者。 2.病例采集及分組：2012年2月至2013年11月于廣州軍區(qū)武漢總醫(yī)院神經(jīng)外科共納入符合上述標準tSAH患者62例,其中男性患者50例,女性患者12例；年齡最小者18歲,最大者65歲,平均年齡為(38±12.6)歲；入院時GCS評分6-8分23例,9-12分39例。按入院順序分為治療組和對照組,各31例。治療組男性患者26例,女性患者5例；年齡18-62歲,平均年齡36歲。對照組男性患者24例,女性患者7例；年齡20-65歲,平均年齡40歲。 3.治療方法：對照組給予促醒、營養(yǎng)神經(jīng)、止血、預(yù)防消化道潰瘍、脫水、預(yù)防感染、鎮(zhèn)靜等常規(guī)治療；治療組在對照組常規(guī)治療的基礎(chǔ)上于實行持續(xù)顱內(nèi)壓監(jiān)測后開始用微量泵靜脈推注尼莫地平注射液(德國拜耳公司,規(guī)格為50ml:10mg),具體劑量依體重而定(對于體重≤70kg者,初始劑量為0.5ml/h,如無顱內(nèi)壓急劇升高、低血壓等不良反應(yīng),2h后改為lmg/h;體重70kg者,初始劑量為1mg/h,如耐受良好,2h后改為2mg/h),每天靜脈給藥劑量24-48mg,靜脈用藥14d后改為口服尼莫地平片(60mg,每日4次；德國拜耳公司,規(guī)格為30mg/片),一個療程為7天,共用藥3個療程。 4.評價指標：入院后行持續(xù)顱內(nèi)壓監(jiān)測14天,分別計取傷后1、3、5、7、10、14天的顱內(nèi)壓平均值；于傷后第1、3、5、7、10、14、21天分別對患者意識狀態(tài)進行GCS評定；于傷后1、3、5、7、14、21天分別行大腦中動脈TCD檢查監(jiān)測大腦中動脈血流速度,血流速度大于120cm/s提示存在CVS；傷后3月隨訪,用GOS進行預(yù)后評定；預(yù)后評定分為良好、中度殘疾、重度殘疾、植物生存、死亡五個檔次。其中持續(xù)植物生存壯態(tài),即指對外界環(huán)境無任何反應(yīng),無任何意識和精神活動；重度致殘即指由于神經(jīng)功能障礙和精神異常,生活不能自理；中度致殘,即指生活可以自理,但由于神經(jīng)功能障礙或精神異常喪失正常工作能力；良好,即指恢復(fù)正常工作,可并發(fā)輕度神經(jīng)功能異常或精神功能異常；而良好、中度殘疾歸為預(yù)后良好,其余情況為預(yù)后不良。試驗結(jié)束后分別對GCS、大腦中動脈血流速度、顱內(nèi)壓及預(yù)后結(jié)果等相應(yīng)指標進行統(tǒng)計學分析。 5.統(tǒng)計學分析：計量資料數(shù)據(jù)采用x±s表示,均采用SPSS13.0統(tǒng)計軟件進行統(tǒng)計學分析,計量資料的比較采用重復(fù)測量方差分析(組間比較：方差齊采用LSD法,方差不齊采用Games-Howell法),計數(shù)資料及率的比較采用x2檢驗,以P0.05為差異有顯著性的判定標準。 結(jié)果： 1.兩組患者GCS評分比較：治療組與對照組入院時的GCS值分別為9.03±1.89、8.97±1.91,兩組患者治療后GCS值均逐漸升高,治療組治療后第3、5、7、10、14、21天的GCS值分別為9.23±2.17、9.68±1.94、10.65±1.6211.87±1.78、12.55±1.52、14.52±0.89,對照組治療后第3、5、7、10、14、21天的GCS值分別為9.10±1.97、9.35±1.89、9.42±1.95、10.35±1.94、11.58±1.82、13.58±1.46,兩組GCS評分差異有統(tǒng)計學意義(F分組=5.612,P0.05),不同時間GCS評分的差異有統(tǒng)計學意義(F時間=73.383,P0.05),分組和時間的交互作用有統(tǒng)計學意義(F交互=2.246,P0.05),7天后治療組明顯高于對照組(P0.05)。 2.兩組患者顱內(nèi)壓比較：在該試驗中,對照組治療前顱內(nèi)壓值為21.65±3.73mmHg,隨后逐步上升,3天后達25.77±3.68mmHg,于治療第5天左右達峰值(27.19±3.80mmHg),隨后開始逐步下降,至2周時回復(fù)至15.74±1.71mmHg,但仍稍高于正常值,而治療組顱內(nèi)壓從傷后23.65±3.37mmHg開始逐步上升,于傷后第3天時達峰值(26.61±3.68mmHg),后逐步下降,兩周后恢復(fù)至正常范圍(11.74±2.78mmHg)兩組患者的顱內(nèi)壓先均有一定幅度上升,隨后均呈下降趨勢,但在時間上治療組明顯早于對照組；兩組顱內(nèi)壓差異有統(tǒng)計學意義(F分組=60.597,P0.05),不同時間顱內(nèi)壓的差異有統(tǒng)計學意義(F時間=157.320,P0.05),分組和時間的交互作用有統(tǒng)計學意義(F交互=28.854,P0.05)。 3.兩組MCA血流速度比較：在試驗中共有38例患者(61.3%)MCA至少經(jīng)歷了一次CVS,而在時間上絕大多數(shù)發(fā)生于傷后5天內(nèi),持續(xù)時間一般不超過14天；治療組CVS發(fā)生率(35.5%,11/31)明顯低于對照組(61.3%,19/31),差異有統(tǒng)計學意義(χ2=4.473,P0.05)。在該設(shè)計試驗中,對照組傷后治療前MCA血流速度為128.45±20.07cm/s,明顯高于正常,3天后達到峰值(132.97±21.28cm/s),治療第5天較前略有下降(129.16±17.42cm/s),但仍處于較高水平,治療第7天顯示血流速度繼續(xù)下降(118.35±14.54cm/s),兩個星期后恢復(fù)至正常范圍(112.13±8.70cm/s),而治療組MCA血流速度從開始治療后并未出現(xiàn)明顯上升,反而呈逐步下降趨勢,并于一周后恢復(fù)至正常范圍(106.90±11.34cm/s),治療組治療3天后傷側(cè)MCA血流速度明顯低于對照組；兩組患者MCA血流速度差異有統(tǒng)計學意義(F分組=9.762,P0.05),不同時間Vp的差異有統(tǒng)計學意義(F時間=76.580,0.05),分組和時間的交互作用有統(tǒng)計學意義(F交互=3.257,P0.05)。 4.兩組患者預(yù)后比較：傷后3月對所有患者采用GOS評分進行隨訪,其中治療組恢復(fù)良好19例(61.3%),中度殘疾7例(22.6%),重度殘疾5例(16.1%)；對照組恢復(fù)良好16例(51.6%),中度殘殘2例(6.5%),重度殘疾13例(41.9%)；治療組預(yù)后良好率(83.9%,26/31)明顯高于對照組(58.1%,18/31)。差異有統(tǒng)計學意義(χ2=5.010,P0.05)。 結(jié)論 本實驗結(jié)果顯示創(chuàng)傷性蛛網(wǎng)膜下腔出血患者早期腦血管痙攣發(fā)生率比較高,其中,對照組明顯高于尼莫地平治療組；尼莫地平治療組預(yù)后良好率明顯高于對照組。這一結(jié)果表明,尼莫地平有助于防治創(chuàng)傷性蛛網(wǎng)膜下腔出血腦血管痙攣的發(fā)生,明顯改善tSAH患者預(yù)后。
[Abstract]:No matter in peacetime or wartime, craniocerebral trauma ranks second in the incidence of all kinds of trauma, second only to limb trauma, and its mortality rate ranks first. In the United States, the incidence of craniocerebral trauma is 200 people per 100,000 population, about 500,000 new cases of craniocerebral trauma every year, of which about 20,000 people die and 30,000 people become disabled. About 600,000 patients suffer from craniocerebral trauma each year, of which 100,000 are dead, resulting in direct and indirect economic losses of more than 10 billion yuan. In clinical cases, 39% - 65% of the patients suffer from craniocerebral trauma combined with SAH. Therefore, after craniocerebral trauma, brain tissue contusion and laceration, small blood vessel injury and hemorrhage in the cerebral basal or surface cortex are directly influxed into the brain. This clinical syndrome of subarachnoid space is defined as traumatic subarachnoid hemorrhage. According to its blood distribution, it can be divided into three types: subarachnoid hemorrhage on brain surface, subarachnoid cistern on skull base and mixed type of arachnoid cistern on brain surface and skull base. Graham et al found that about 90% of the patients died of traumatic brain injury had ischemic changes in brain tissue, while the incidence of CVS was as high as 67% in patients with tSAH. Hanlon et al. confirmed that traumatic subarachnoid hemorrhage was one of the most common symptoms in patients with severe brain injury. Nimodipine is a 1,4-dihydropyridine calcium channel antagonist with high liposolubility, which can smoothly cross the blood-brain barrier, selectively block the opening of calcium channel on the cell membrane, reduce the influx of extracellular calcium ions, and inhibit cerebrovascular diseases. Smooth muscle contraction, while enhancing the activity of Ca2+-ATPase, increasing intracellular calcium excretion, reducing intracellular calcium overload, protecting nerve cells, and nimodipine is highly selective to cerebrovascular, improve cerebral artery blood flow is far greater than the effect of peripheral blood vessels, the brain injury area perfusion of insufficient parts of the increase is usually high. Previous studies have confirmed that nimodipine is the only effective drug with evidence-based medical support that has preventive and therapeutic effects on CVS after aSAH. However, there is no definite evidence that nimodipine has the same effect on CVS caused by tSAH. The conclusion is made.
objective
Continuous intracranial pressure monitoring, TCD, GCS, GOS were used to analyze the clinical effect of nimodipine in preventing CVS after tSAH and improving the prognosis of tSAH, so as to provide theoretical basis for its clinical application.
1. Inclusion and exclusion criteria: (1) Inclusion criteria: acute craniocerebral injury, admission within 6 hours after injury; head CT showed subarachnoid hemorrhage; 320 row head CT angiography excluded aneurysm rupture and hemorrhage; supratentorial hematoma volume 30 ml, subtentorial hematoma 10 ml, midline shift 5 mm; age 18-65 years; admission GCS score 6-12 points. (2) Exclusion criteria Gunshot injury and open craniocerebral injury; severe diffuse axonal injury with severe hepatorenal insufficiency; systolic blood pressure below 100 mmHg for more than 1 hour; pregnant women; patients with a history of nicardipine or other calcium antagonists used in clinical trials two weeks prior to onset of the disease; and patients whose condition changes halfway require craniotomy or discontinuation of the trial A person.
2. Case collection and grouping: From February 2012 to November 2013 in Wuhan General Hospital of Guangzhou Military Region, 62 patients with tSAH were enrolled, including 50 males and 12 females; the youngest was 18 years old, the oldest was 65 years old, with an average age of (38 + 12.6); the GCS score at admission was 6-8 in 23 cases, and 9-12 in 39 cases. The treatment group consisted of 26 males and 5 females, aged 18-62 with an average age of 36. The control group consisted of 24 males and 7 females, aged 20-65 with an average age of 40.
3. Treatment: The control group was given routine treatment such as wake-up stimulation, nerve nutrition, hemostasis, prevention of gastrointestinal ulcer, dehydration, prevention of infection, sedation, etc. The treatment group was given Nimodipine Injection by micro-pump after continuous intracranial pressure monitoring on the basis of routine treatment in the control group (German Bayer Company, specifications 50ml:10mg). Body dose depends on body weight (for those with body weight less than 70 kg, the initial dose is 0.5 ml/h, if no adverse reactions such as rapid increase of intracranial pressure, hypotension, etc., and then changed to lmg/h after 2 hours; for those with body weight of 70 kg, the initial dose is 1 mg/h, if tolerated well, changed to 2 mg/h after 2 hours), the daily intravenous dose is 24-48 mg, and nimodipine tablets are orally taken after 14 days (60 mg, daily). The 4 time; Bayer company in Germany, specifications for 30mg/ tablets), a course of treatment for 7 days, sharing drugs 3 courses.
4. Evaluation indicators: Continuous intracranial pressure monitoring was performed on 14 days after admission, and the mean intracranial pressure was calculated on 1, 3, 5, 7, 10 and 14 days after injury; GCS was assessed on the first, 3, 5, 7, 10, 14 and 21 days after injury respectively; middle cerebral artery TCD was performed on 1, 3, 5, 7, 14 and 21 days after injury to monitor the blood flow velocity of middle cerebral artery. CVS was indicated at 120cm/s, followed up at 3 months after injury, and prognosis was assessed by GOS. The prognosis was divided into five grades: good, moderate, severe, vegetative survival and death. And mental disorders, life can not be self-care; moderate disability, that is, life can be self-care, but because of neurological dysfunction or mental disorders loss of normal working ability; good, that is, to return to normal work, can be accompanied by mild neurological dysfunction or mental dysfunction; and good, moderate disability is classified as a good prognosis, the rest of the prognosis is not good After the experiment, GCS, middle cerebral artery blood flow velocity, intracranial pressure and prognosis were statistically analyzed.
5. Statistical analysis: The data of measurement were expressed by X + s, and all were analyzed by SPSS13.0 statistical software. The comparison of measurement data was made by repeated measurement analysis of variance (LSD method was used for all variances, Games-Howell method for all variances). Criterion of sex.
Result:
1. Comparison of GCS scores between the two groups: The GCS values of the treatment group and the control group at admission were 9.03 (+ 1.89), 8.97 (+ 1.91) respectively. After treatment, the GCS values of the two groups increased gradually. The GCS values of the treatment group on the 3rd, 5th, 7th, 10th, 14th and 21st days after treatment were 9.23 (+ 2.17), 9.68 (+ 1.94), 10.65 (+ 1.6211.87) + 1.78, 12.55 (+ 1.52), 14.52 (+ 0.89), respectively. The GCS values of 14 and 21 days were 9.10 (+ 1.97), 9.35 (+ 1.89), 9.42 (+ 1.95), 10.35 (+ 1.94), 11.58 (+ 1.82) and 13.58 (+ 1.46), respectively. There were significant differences in GCS scores between the two groups (F group = 5.612, P 0.05). There were significant differences in GCS scores between the two groups (F time = 73.383, P 0.05), and the interaction between groups and time (F interaction = 2.246, P 0.05), 7. Days later, the treatment group was significantly higher than that of the control group (P0.05).
2. Comparison of intracranial pressure between the two groups: In this experiment, the intracranial pressure of the control group before treatment was 21.65 + 3.73 mmHg, then gradually increased, and reached 25.77 + 3.68 mmHg three days later, peaked at about 5 days after treatment (27.19 + 3.80 mmHg), then began to gradually decrease, and returned to 15.74 + 1.71 mmHg at 2 weeks, but still slightly higher than the normal value. The intracranial pressure of the two groups increased to a certain extent at first and then decreased to a certain extent at the end of two weeks, but the intracranial pressure of the treatment group was significantly earlier than that of the control group. There was statistical significance (F group = 60.597, P 0.05), the difference of intracranial pressure at different time was statistically significant (F time = 157.320, P 0.05), and the interaction between group and time was statistically significant (F interaction = 28.854, P 0.05).
3. Comparison of MCA blood flow velocity between the two groups: 38 patients (61.3%) experienced at least one CVS in the trial, and most of them occurred within 5 days after injury, lasting no more than 14 days; the incidence of CVS in the treatment group (35.5%, 11/31) was significantly lower than that in the control group (61.3%, 19/31), the difference was statistically significant (2 = 4.473, P 0.05). In the design test, the MCA blood flow velocity of the control group was 128.45 (+ 20.07 cm/s) before and after treatment, which was significantly higher than that of the normal control group. The MCA blood flow velocity peaked at 132.97 (+ 21.28 cm/s) after 3 days, and decreased slightly at the 5th day after treatment (129.16 (+ 17.42 cm/s), but remained at a higher level. On the 7th day of treatment, the MCA blood flow velocity continued to decrease (118.35 (+ 14.54 cm/s) and returned to normal level two weeks later. The blood flow velocity of MCA in the treatment group did not increase significantly from the beginning of treatment, but decreased gradually, and returned to normal range after one week (106.90 (+ 11.34 cm / s). The blood flow velocity of MCA on the injured side in the treatment group was significantly lower than that in the control group after three days of treatment. Significance (F group = 9.762, P 0.05), different time Vp difference was statistically significant (F time = 76.580, 0.05), grouping and time interaction was statistically significant (F interaction = 3.257, P 0.05).
4. Comparison of prognosis between the two groups: All patients were followed up with GOS score at 3 months after injury, 19 cases (61.3%), 7 cases (22.6%) with moderate disability and 5 cases (16.1%) with severe disability in the treatment group; 16 cases (51.6%) with good recovery in the control group, 2 cases (6.5%) with moderate disability and 13 cases (41.9%) with severe disability in the control group; and 83.9% with good prognosis in the treatment group (26/31) was obvious. Higher than the control group (58.1%, 18/31). The difference was statistically significant (x 2=5.010, P0.05).
conclusion
The results showed that the incidence of early cerebral vasospasm in patients with traumatic subarachnoid hemorrhage was higher than that in the nimodipine treatment group, and the good prognosis rate in the nimodipine treatment group was higher than that in the control group. The occurrence of tSAH significantly improved the prognosis of patients.
【學位授予單位】：南方醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R651.15

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